MODULATION OF GABA(C) RECEPTORS IN RAT RETINAL BIPOLAR CELLS BY PROTEIN-KINASE-C

1. The intracellular phosphorylation of bicuculline- and baclofen-insensitive GABA(c), receptors was investigated in rat retinal bipolar cells. The cells were recorded in organotypic slice cultures by using the whole-cell configuration of the patch-clamp technique. 2. Peak GABA responses recorded in the presence of bicuculline decreased with repetitive GABA applications. Intracellular application of the phorbol ester, phorbol 12-myristate, 13-acetate (PMA) increased this run-down, whilst it was prevented by both tamoxifen and phosphatase. 3. Perfusing the cells extracellularly with L-AP4, trans-(+/-)-1-amino-1,3-cyclopentane dicarboxylate (ACPD) or a-methyl serotonin accelerated the run-down of GABA, responses. 4. Modulation of GBBA(c) responses could be induced by intracellular application of GTP gamma S, indicating involvement of G-proteins in the transduction cascade. 5. These results suggest that retinal GABA(c), receptors in bipolar cells are modulated by protein kinase C. Receptors which stimulate phospholipase C, presumably via G(i) or G(o), such as some of the metabotropic glutamate receptors or the 5-HT2 receptor, appear to be linked to this regulatory pathway.